The use of mammography, as an important means for the early detection of human breast cancer, has become controversial in view of the risk of inducing breast cancer that has become associated with radiation exposure. Studies of the A-bomb survivors at Hiroshima and Nagasaki, and the excess risk associated with fluoroscopic procedures involving the incidental irradiation of mammary tissue, make clear that, in terms of tumorigenesis, mammary tissue is radioresponsive. This evidence from human studies is in part supported by radiation studies with rats; in particular, with X-ray dose fractionation adenocarcinoma induction appears to increase while total breast tumor induction decreases. The limited data available from cultured cells thus far suggest that, for an interfraction interval up to 8 hours, the frequency of neoplastic transformation is increased when a single dose less than approximately 100 rad is split into two doses. Using cells in culture we propse to extend studies of the dependence of frequencies of neoplastic transformation on radiation dose fractionation in order that the extent of the biophysical extrapolation to mammography can be reduced. C3H mouse 10T1/2 cells will be used for these initial measurements. The fractionation dependence of mutation induction in rodent and human cells will be examined in order to help reduce the biological extrapolation involved. Fractionation studies will also be conducted with epithelial cells in culture, and particularly with such cells derived from mammary gland tissue, as and when adequate cell systems and suitable assays become available. In addition to affording information of a practical nature, these studies should permit insights into the role of repair processes in the radiation induction of altered cell properties.